Incorporation of Beclomethasone Dipropionate into Polyethylene Glycol‐Diacyl Lipid Micelles as a Pulmonary Delivery System

Abstract

Strategy, Management and Health Policy Enabling Technology, Genomics, ProteomicsPreclinical ResearchPreclinical Development Toxicology, Formulation Drug Delivery, PharmacokineticsClinical Development Phases I‐III Regulatory, Quality, ManufacturingPostmarketing Phase IV Nebulized corticosteroid drugs have several shortcomings due to their poor water solubility and nonoptimal deposition pattern. The aims of this study were to investigate the in vitro and in vivo characteristics of beclomethasone dipropionate (BDP)‐loaded sterically stabilized phospholipid nanomicelles (SSMs) of a polyethylene glycol–phosphatidylethanolamine conjugate as a pulmonary delivery system. The particle size distribution and zeta potential measurements were 14.60 ± 1.11 nm and −46.94 ± 3.27 mV, respectively. The solubility of BDP was highly improved by at least 1,300 times its actual solubility. No chemical interaction was found between the PEGylated polymer and BDP as demonstrated by the Fourier transform infrared results. The in vitro aerodynamic of the aerosolized BDP‐SSMs using an Omron nebulizer showed an improvement in the aerodynamic values, with a significant deposition in the seven‐stage Next Generation Impactor. The BDP‐SSMs showed a prolonged dissolution profile of about 3 days. Intratracheal administration of the BDP‐SSMs (1 mg/kg) 12 or 23 h before a challenge in the asthmatic rat model led to a significant reduction in the inflammatory cell counts in bronchoalveolar lavage fluid samples compared with the administration of solubilized BDP. The SSM system appears to be an effective way of improving the therapeutic index of nebulized, poorly soluble corticosteroids.

The use of heat to deliver fentanyl via pulmonary drug delivery

“…2 . The use of micelles for pulmonary drug delivery has mostly included treatments for asthma ( Pellosi et al, 2018 ; Sahib et al, 2012 ; Triolo et al, 2017 ). Sahib et al successfully loaded nanomicelles with beclomethasone dipropionate (BDP), a steroid for treating asthma.…”

Nano-Therapeutics for the Lung: State-of-the-Art and Future Perspectives

“…Nanocarriers can be used to improve the solubility and delivery efficiency of these drugs. For example, poly(ethylene glycol)–phosphatidyl-ethanolamine micelles have been developed as a pulmonary delivery system to improve the solubility of encapsulated beclomethasone dipropionate up to 1,300 times, and provide extended anti-inflammatory activity compared to the administration of solubilized drug at the same dose [85]. PLGA nanoparticles have been used to improve pulmonary delivery of the anti-fibrotic drug pirfenidone [86].…”

Realization of polyaspartamide-based nanoparticles and in vivo lung biodistribution evaluation of a loaded glucocorticoid after aerosolization in mice

“…Indeed, it has been shown that BDP incorporated into sterically stabilized phospholipidbased micelles of 1,2-Distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxy-PEG2000 (PEG2000-DSPE), administered intratracheally in the asthmatic rat model, led to a significant reduction in the bronchoalveolar lavage fluid (BALF) inflammatory cell counts as compared with free BDP (Sahib et al, 2012).…”